环糊精手性固定相的合成及对手性农药中间体的分离研究
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摘要
在手性农药的研究领域中，手性分离方法是一个十分重要的研究课题。其中使用手性固定相的毛细管气相色谱法以其简捷、灵敏的优点，成为众多手性分离技术常用的方法。
本论文主要集中于各种新型环糊精衍生物固定相的研制及其在手性农药中间体分离中的应用研究，并探讨了其手性分离机理。研究分两部分：
第一部分，我们在总结和分析了气相色谱β-环糊精衍生物固定相的最新研究进展和手性农药在色谱中分离的基础之上，以手性固定相设计的基本原理和超分子化学的基本观点为指导，设计、合成了两个系列共七种新型β-环糊精衍生物手性固定相。这些化合物的结构得到IR和~1HNMR确证，其结构的新颖性也经STN国际联机检索。
第二部分，我们采用静态法制备了十根毛细管气相色谱柱，包括七根β-环糊精衍生物手性固定相和三根常规固定相。并研究了它们的色谱性能。结果如下：
(1)在所制备的毛细管气相色谱柱中，有些色谱柱有较好的涂渍性能，柱效达到2000块／米以上，而另外一些色谱柱涂渍性很差，柱效低于100块／米。经过比较发现色谱柱涂渍性能与固定相的物理性能有很大关系。通过研究β-环糊精衍生物手性固定相的极性，发现它们属于中等偏弱极性固定相。其中H2-CD极性最强，SP1-CD极性最弱。
(2)经过对不同极性化合物的代表Grob试剂的分离研究，发现多数β-环糊精衍生物色谱柱对Grob具有良好的色谱分离能力，尤其对芳香族位置异构体表现出良好的分离效果。其中对在SE-54，PEG-20M固定相上较难分离的二甲苯、氯甲苯等在H1-CD，P-CD，SP1-CD等固定相上得到良好分离。对未见有过分离报道的氯苯胺、硝苯胺等二取代芳香族位置异构体也有较好的分离。
(3)在普通手性化合物的分离中，我们重点测试了三个固定相(H1-CD，P-CD，SP1-CD)。它们都表现出良好的手性分离能力，共分离包括2-氯丙酸甲酯、乳酸甲酯、α-苯乙胺等20多种手性化合物。
(4)在对手性农药中间体的分离中，H1-CD表现出了良好的手性拆分能力。不仅能将菊酸甲酯等含2个手性中心有4个对映异构体的化合物分离开，而且能将菊酸仲丁酯、菊酰仲丁胺等含3个手性中心有8个对映异构体的化合物分开。特别是对含胺基的农药衍生物有很好的分离能力。共分离了11种拟除虫菊酸衍生物。其中有6种手性农药衍生物的分离未见文献报道。
(5)我们从热力学角度对制备的β-环糊精衍生物固定相的手性分离机理进行了探讨。通过热力学参数计算，发现弱相互作用力在手性分离过程中起了重要的作用。
The separation of enantiomers has become very important in chiral insecticides study. Capillary gas chromatography using chiral stationary phase is a simple and convenient way for enantioseparation and a powerful tool among many analysis methods.
The purpose of study is to investigate the synthesis and application of new cyclodextrin derivatives as stationary phase on separation of chiral insecticide's intermediates. The work can be divided into two parts:
Firstly, after reviewing the importance of cyclodextrin derivatives(CDs) as stationary phase in capillary gas chromatography and the advance in separtion of chiral insecticides, we find it is probable to separte the chiral insecticides by modifying the CDs' structure. So, two series of CDs (total seven compounds) are designed and prepared, according to the fundmental principle designing for chiral stationary phase. The structures of these compounds are confirmed by IR and 'HNMR, and they are novel, which have deen searched through STN.
Secondly, ten capillary gas chromatographic columns are prepared with static method, including seven CDs and three conventional stationary phase. Their chromatographic performances are as follows:
(1) Some of the prepared CDs chiral stationary phases, have good film-forming ability and their column efficiency are more than 2000 plate/m, but others have poor film-forming ability. The polarity of novel CDs chiral stationary phases are tested and compared with the same kind CDs chiral stationary phases reported. The results show their polarity are moderate. The polarity of H1-CD is the strongest, SP1-CD the weakest among them.
(2) The separation of new CDs chiral stationary phases for general compound is examined with Grab. The results display strong retention and favourable separation for general compounds, especially for aromatic isomers, such as xylene, cresol and chlorotolune, which are difficult to be separated on SE-54 and PEG-20M.
(3) It is found that some chiral columns, including H-CD, P-CD and SP1-CD, possess excellent enantioseparation's ability. More than twenty general chiral compounds are separated, such as 2-chloropropionic acid methyl ester, allethyone acetate and propargyllone acetate etc.
(4) We study enantioseparation of some chiral insecticide's intermediates on H1-CD. Eleven pyrethroid derivatives are separated. The results show the pyrethroid derivatives are well separated, including pyrethroic acid methyl esters (containing two chiral center and four chiral isomers), pyrethroic acid sec-butyl esters (containing three chiral center and eight chiral isomers).
(5) The mechanism of enantioseparation is discussed from the view point of thermodynamics simply.
本论文主要集中于各种新型环糊精衍生物固定相的研制及其在手性农药中间体分离中的应用研究，并探讨了其手性分离机理。研究分两部分：
第一部分，我们在总结和分析了气相色谱β-环糊精衍生物固定相的最新研究进展和手性农药在色谱中分离的基础之上，以手性固定相设计的基本原理和超分子化学的基本观点为指导，设计、合成了两个系列共七种新型β-环糊精衍生物手性固定相。这些化合物的结构得到IR和~1HNMR确证，其结构的新颖性也经STN国际联机检索。
第二部分，我们采用静态法制备了十根毛细管气相色谱柱，包括七根β-环糊精衍生物手性固定相和三根常规固定相。并研究了它们的色谱性能。结果如下：
(1)在所制备的毛细管气相色谱柱中，有些色谱柱有较好的涂渍性能，柱效达到2000块／米以上，而另外一些色谱柱涂渍性很差，柱效低于100块／米。经过比较发现色谱柱涂渍性能与固定相的物理性能有很大关系。通过研究β-环糊精衍生物手性固定相的极性，发现它们属于中等偏弱极性固定相。其中H2-CD极性最强，SP1-CD极性最弱。
(2)经过对不同极性化合物的代表Grob试剂的分离研究，发现多数β-环糊精衍生物色谱柱对Grob具有良好的色谱分离能力，尤其对芳香族位置异构体表现出良好的分离效果。其中对在SE-54，PEG-20M固定相上较难分离的二甲苯、氯甲苯等在H1-CD，P-CD，SP1-CD等固定相上得到良好分离。对未见有过分离报道的氯苯胺、硝苯胺等二取代芳香族位置异构体也有较好的分离。
(3)在普通手性化合物的分离中，我们重点测试了三个固定相(H1-CD，P-CD，SP1-CD)。它们都表现出良好的手性分离能力，共分离包括2-氯丙酸甲酯、乳酸甲酯、α-苯乙胺等20多种手性化合物。
(4)在对手性农药中间体的分离中，H1-CD表现出了良好的手性拆分能力。不仅能将菊酸甲酯等含2个手性中心有4个对映异构体的化合物分离开，而且能将菊酸仲丁酯、菊酰仲丁胺等含3个手性中心有8个对映异构体的化合物分开。特别是对含胺基的农药衍生物有很好的分离能力。共分离了11种拟除虫菊酸衍生物。其中有6种手性农药衍生物的分离未见文献报道。
(5)我们从热力学角度对制备的β-环糊精衍生物固定相的手性分离机理进行了探讨。通过热力学参数计算，发现弱相互作用力在手性分离过程中起了重要的作用。
The separation of enantiomers has become very important in chiral insecticides study. Capillary gas chromatography using chiral stationary phase is a simple and convenient way for enantioseparation and a powerful tool among many analysis methods.
The purpose of study is to investigate the synthesis and application of new cyclodextrin derivatives as stationary phase on separation of chiral insecticide's intermediates. The work can be divided into two parts:
Firstly, after reviewing the importance of cyclodextrin derivatives(CDs) as stationary phase in capillary gas chromatography and the advance in separtion of chiral insecticides, we find it is probable to separte the chiral insecticides by modifying the CDs' structure. So, two series of CDs (total seven compounds) are designed and prepared, according to the fundmental principle designing for chiral stationary phase. The structures of these compounds are confirmed by IR and 'HNMR, and they are novel, which have deen searched through STN.
Secondly, ten capillary gas chromatographic columns are prepared with static method, including seven CDs and three conventional stationary phase. Their chromatographic performances are as follows:
(1) Some of the prepared CDs chiral stationary phases, have good film-forming ability and their column efficiency are more than 2000 plate/m, but others have poor film-forming ability. The polarity of novel CDs chiral stationary phases are tested and compared with the same kind CDs chiral stationary phases reported. The results show their polarity are moderate. The polarity of H1-CD is the strongest, SP1-CD the weakest among them.
(2) The separation of new CDs chiral stationary phases for general compound is examined with Grab. The results display strong retention and favourable separation for general compounds, especially for aromatic isomers, such as xylene, cresol and chlorotolune, which are difficult to be separated on SE-54 and PEG-20M.
(3) It is found that some chiral columns, including H-CD, P-CD and SP1-CD, possess excellent enantioseparation's ability. More than twenty general chiral compounds are separated, such as 2-chloropropionic acid methyl ester, allethyone acetate and propargyllone acetate etc.
(4) We study enantioseparation of some chiral insecticide's intermediates on H1-CD. Eleven pyrethroid derivatives are separated. The results show the pyrethroid derivatives are well separated, including pyrethroic acid methyl esters (containing two chiral center and four chiral isomers), pyrethroic acid sec-butyl esters (containing three chiral center and eight chiral isomers).
(5) The mechanism of enantioseparation is discussed from the view point of thermodynamics simply.
引文
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